Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

The Cost and the Value of Stroke Care in Greece: Results from the SUN4P Study.

The aim of this study was to measure the one-year total cost of strokes and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first-ever acute strokes, hemorrhagic strokes, and ischemic strokes, (ICD-10 codes: I61, I63, and I64) admitted within 48 h of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality, and informal care costs were considered. We used an annual time horizon, including all costs for 2021, irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at EUR 343.1 mil. a year in 2021, (EUR 10,722/patient or EUR 23,308 per QALY). Out of EUR 343.1 mil., 53.3% (EUR 182.9 mil.) consisted of direct healthcare costs, representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at EUR 160.2 mil. The mean productivity losses were estimated to be 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality, and 42.4 days lost due to informal caregiving by family members. This study highlights the burden of stroke and underlines the need for stakeholders and policymakers to re-organize stroke care and promote interventions that have been proven cost-effective.

Global Economic Burden Associated with Chronic Kidney Disease: A Pragmatic Review of Medical Costs for the Inside CKD Research Programme.

INTRODUCTION: Chronic kidney disease (CKD) is a progressive disease of growing prevalence, posing serious concerns for global public health. While the economic burden of CKD is substantial, data on the cost of CKD is limited, despite growing pressures on healthcare systems. In this review, we summarise the available evidence in 31 countries and regions and compile a library of costing methodology and estimates of CKD management and disease-associated complications across 31 countries/regions within the Inside CKD programme. METHODS: We collected country/region-specific CKD costs via a pragmatic rapid literature review of local literature and engagement with local experts. We extracted cost data and definitions from identified sources for CKD stages G3a-5, kidney failure with replacement therapy by modality, covering haemodialysis, peritoneal dialysis, and kidney transplants, and disease-associated complications in local currency, converted to United States dollars (USD) and inflated to 2022. RESULTS: Annual direct costs associated with CKD management rose by an average factor of 4 in each country/region upon progression from stage G3a to G5. Mean annual costs per patient increased considerably more from early stages versus dialysis (stage G3a, mean: $3060 versus haemodialysis, mean: $57,334; peritoneal dialysis, mean: $49,490); with estimates for annual costs of transplant also substantially higher (incident: $75,326; subsequent: $16,672). The mean annual per patient costs of complications were $18,294 for myocardial infarction, $8463 for heart failure, $10,168 for stroke and $5975 for acute kidney injury. Costing definitions varied widely in granularity and/or definition across all countries/regions. CONCLUSION: Globally, CKD carries a significant economic burden, which increases substantially with increasing disease severity. We identified significant gaps in published costs and inconsistent costing definitions. Cost-effective interventions that target primary prevention and disease progression are essential to reduce CKD burden. Our results can be used to guide cost collection and facilitate better comparisons across countries/regions to inform healthcare policy.

Epidemiology, reperfusion management, and outcomes of patients with myocardial infarction in Greece: The ILIAKTIS study.

OBJECTIVE: Acute myocardial infarction (AMI) is one of the leading causes of death; however, updated data regarding clinical presentation and current management are missing in Greece. This study aimed to prospectively record the demographic and clinical characteristics of a representative sample of patients suffering from AMI, their management, and short-term outcomes. METHODS: ILIAKTIS is a national, prospective, multicenter, noninterventional study conducted under the auspices of Hellenic Society of Cardiology (HCS) and the European Initiative Stent - Save a Life. From 1st April 2020 to 30th June 2020, consecutive adult patients with STEMI or NSTEMI were enrolled in the 50 participating hospitals, appropriately selected to match the geographical and population distribution in the Greek territory. RESULTS: In total, 1862 patients (mean age: 64.2 ± 13.2 yrs.; 77.2% males) with AMI were enrolled. More patients presented with NSTEMI (56.8%) than with STEMI (43.2%). Primary PCI (pPCI) was the preferable treatment option for STEMI patients in PCI-hospitals (76.9% vs. 39.9% for non-PCI, p < .001) and thrombolysis in non-PCI-hospitals (47.3% vs. 17.9% for PCI-hospitals, p < .001). The mean length of hospital stay was 5.6 days. In-hospital mortality was less likely in NSTEMI compared to that in STEMI patients (aOR = 0.30; 95% CI 0.18 to 0.49). Patients initially admitted in non-PCI-hospitals showed increased risk for in-hospital (aOR = 2.29; 95% CI 1.20 to 4.42) and 30-day mortality (aOR = 1.88; 95% CI 1.20 to 2.96). CONCLUSION: This study shows that the proportion of STEMI and NSTEMI patients managed interventionally has significantly increased, resulting in better clinical outcomes compared to previous Greek surveys.

Estimation of the economic burden of atrial fibrillation-related stroke in Greece.

BACKGROUND: Stroke is aleading cause of death and disability, with atrial fibrillation (AF) being among key risk factors and AF-related stroke inflicting significant burden on healthcare systems and society. The present study was undertaken for estimating the total annual socioeconomic burden of AF-related stroke in Greece and identifying the key cost contributors. RESEARCH DESIGN AND METHODS: A cost-of-illness model was developed for estimating the total annual economic burden of AF-related stroke in Greece, from asocietal perspective (year 2018). Atargeted literature review and an advisory board consisting of key experts in the management of AF and AF-related stroke were performed for collecting local resource use and epidemiological data. RESULTS: The total annual socioeconomic burden of AF-related stroke was estimated at €175million, in 2018. Direct and indirect costs accounted for 59% and 41%, respectively. Main contributors were informal care (21.1%), patients' productivity losses (19.7%) and hospitalizations (15.0%), accounting for more than half of the total costs of AF-related stroke events.Conclusion: A F-related stroke imposes asignificant socioeconomic burden in Greece. Despite results relying on estimations, it seems that ensuring efficient reallocation of resources in appropriate prevention and early intervention strategies could decrease AF-related stroke's burden but also enhance healthcare systems' efficiency. ABBREVIATIONS: AF=atrial fibrillation.

BeyondSilos, a Telehealth-Enhanced Integrated Care Model in the Domiciliary Setting for Older Patients: Observational Prospective Cohort Study for Effectiveness and Cost-Effectiveness Assessments.

BACKGROUND: Information and communication technology may provide domiciliary care programs with continuity of care. However, evidence about the effectiveness and cost-effectiveness of information and communication technology in the context of integrated care models is relatively scarce. OBJECTIVE: The objective of our study was to provide evidence on the clinical effectiveness and cost-effectiveness of the BeyondSilos project for patients enrolled in the Badalona city pilot site in Spain. METHODS: A quasi-experimental study was used to assess the cost-effectiveness of information and communication technology-enhanced integration of health and social care, including the third sector (intervention), compared to basic health and social care coordination (comparator). The study was conducted in Badalona between 2015 and 2016. Participants were followed for 8 months. RESULTS: The study included 198 patients: 98 in the intervention group and 100 in the comparator group. The mean Barthel index remained unchanged in the intervention group (mean change 0.14, 95% CI -4.51 to 4.78; P=.95) but decreased in the comparator group (mean change -3.23, 95% CI -5.34 to -1.11; P=.003). Instrumental Activities of Daily Living significantly decreased in both groups: mean changes of -0.23 (95% CI -0.44 to -0.02; P=.03) and -0.33 (95% CI -0.46 to -0.20; P<.001) in the intervention and comparator groups, respectively. No differences were found in the Geriatric Depression Scale (intervention: mean change 0.28, 95% CI -0.44 to 1.01, P=.44; comparator: mean change -0.29, 95% CI -0.59 to 0.01, P=.06). The intervention showed cost-effectiveness (incremental cost-effectiveness ratio €6505.52, approximately US $7582). CONCLUSIONS: The information and communication technology-enhanced integrated domiciliary care program was cost-effective. The beneficial effects of this approach strongly rely upon the commitment of the professional staff involved. TRIAL REGISTRATION: ClinicalTrials.gov NCT03111004; http://clinicaltrials.gov/ct2/show/ NCT03111004.

The effectiveness of remote monitoring of elderly patients after hospitalisation for heart failure: The renewing health European project.

Background: The effectiveness of remote monitoring (RM) in the management of the elderly after hospitalisation for heart failure (HF) is uncertain. Methods and results: Randomized trial (2:1 design) comparing RM with usual care (UC) in patients >65 years old, hospitalised in the previous 3 months for HF with left ventricular ejection fraction <40% or >40% plus BNP > 400 (or NT-proBNP >1500); the primary end-point (PE) was the combined 12-month incidence of death by any cause or at least one hospital readmission for HF. Overall, 229 and 110 pts were enrolled in the RM and UC group, respectively; in the intention-to-treat analysis, the PE was reached in 101 (44.1%) and 51 (46.4%) patients in the RM and UC group respectively (p = 0.78), with no difference in mortality (24.0% vs 21.8%, p = 0.097) or in the proportion of patients with at least one rehospitalisation for HF (34.5% vs 39.1%, p = 0.48). Quality of life, secondary end-point measured by SF36v2 scores, was significantly improved in the RM group, both in physical (2.63 score difference, p < 0.0001) and mental (1.69 score difference, p = 0.04) components. In the on-treatment analysis comparing 190 patients that ultimately received RM with the 149 remaining patients, the primary end-point was reached in 40.0% vs 51.0% (p = 0.055), respectively. Conclusion: In the intention-to-treat analysis, during the 12-month follow up of elderly patients hospitalised for HF, remote monitoring had no impact on the primary end-point but it significantly improved patients' quality of life. In the on-treatment analysis a trend for improving the PE was observed in the RM group.

Association between copayment, medication adherence and outcomes in the management of patients with diabetes and heart failure.

OBJECTIVE: To determine the association between copayment, medication adherence and outcomes in patients with Heart failure (HF) and Diabetes Mellitus (DM). METHODS: PubMed, Scopus and Cochrane databases were searched using combinations of four sets of key words for: drug cost sharing; resource use, health and economic outcomes; medication adherence; and chronic disease. RESULTS: Thirty eight studies were included in the review. Concerning the direct effect of copayment changes on outcomes, the scarcity and diversity of data, does not allow us to reach a clear conclusion, although there is some evidence indicating that higher copayments may result in poorer health and economic outcomes. Seven and one studies evaluating the relationship between copayment and medication adherence in DM and HF population, respectively, demonstrated an inverse statistically significant association. All studies (29) examining the relationship between medication adherence and outcomes, revealed that increased adherence is associated with health benefits in both DM and HF patients. Finally, the majority of studies in both populations, showed that medication adherence was related to lower resource utilization which in turn may lead to lower total healthcare cost. CONCLUSION: The results of our systematic review imply that lower copayments may result in higher medication adherence, which in turn may lead to better health outcomes and lower total healthcare expenses. Future studies are recommended to reinforce these findings.

Telemonitoring of Type 2 Diabetes Mellitus in Italy.

BACKGROUND: Type 2 diabetes mellitus (DM) affects 382 million people worldwide. INTRODUCTION: This study aimed at assessing whether telemonitoring (TM) of DM patients improves health-related quality of life (HRQoL). MATERIALS AND METHODS: As part of the RENEWING HEALTH project, 299 DM patients with HbA1c >7.0% were enrolled in a randomized controlled trial, with 208 patients in the TM group and 91 patients in the usual-care group. TM electronically transmitted glucose measurements to physicians during a 12-month follow-up. The SF-36v2 questionnaire was used to assess HRQoL. RESULTS: In a total of 243 patients analyzed, the study did not identify any clinically important improvement in HRQoL, our primary endpoint. There was no statistically significant difference in HbA1c between the two groups; however, outpatient visits and planned hospitalizations were significantly reduced in the TM group (p < 0.0001 and p = 0.02). DISCUSSION: The results regarding HRQoL might be, at least in part, an artifact stemming from the criteria used to select patients. TM reduced ambulatory visits and planned hospital admissions, an important result that plausibly reflects the fact that clinicians can strictly monitor their patients' health status without face-to-face contacts. CONCLUSIONS: Enhancement of HRQoL should represent the most critical goal of DM healthcare delivery. Effects of TM on HRQoL of diabetic patients should be studied further.

The medical and socioeconomic burden of heart failure: A comparative delineation with cancer.

Cardiovascular disease and cancer represent the two leading causes of death in the Western World. Still, cardiovascular disease causes more deaths and more hospitalizations than cancer. Although mortality rates of both conditions are generally declining, this is not true for heart failure (HF). The prevalence of HF is increasing, although its incidence has been stabilized, mainly because of the population aging. The survival of patients with HF is overall worse than those with cancer. In addition, HF failure is the most common reason for hospitalization in the elderly, while hospitalization for HF is followed by adverse prognosis and represents the main contributor to the huge financial expenditure caused by the syndrome. The outcome of HF patients and thus its medical and socioeconomic burden may be improved by the more efficient in-hospital management of patients, the enhancement of adherence to guideline-recommended therapies, the identification and treatment of comorbid conditions and the introduction of more effective medical therapies.

Economic evaluation of a single-pill triple antihypertensive therapy with valsartan, amlodipine, and hydrochlorothiazide against its dual components.

The aim of this study was to compare the cost-utility of the first available single-pill triple combination antihypertensive therapy containing valsartan (V), amlodipine (A) and hydrochlorothiazide (H), with each of the same components dual combinations in patients with moderate to severe hypertension. A Markov model with eight health states was constructed. The short-term effect of antihypertensive treatment on blood pressure was extrapolated through the Hellenic SCORE and Framingham risk equations, estimating the long-term survival and quality-adjusted life-years (QALYs) saved. Costs and outcomes were evaluated over lifetime, divided into annual cycles and discounted at 3.0 % with 2013 as reference year. The analysis was conducted by the Greek third-party-payer perspective. The triple combination treatment cost was estimated at €16,525 compared to €15,480 for V/A, €14,125 for V/H and €11,690 for A/H. The QALYs saved with the triple combination were 12.76 vs. 12.64, 12.61 and 12.38 for double combinations respectively. The incremental cost-effectiveness ratio of the triple combination versus V/A and A/H was far lower than the Greek GDP per capita (€8,690/QALY and €12,695/QALY, respectively) and really close for V/H (€16,192/QALY), suggesting V/A/H combination to be cost-effective. Extensive sensitivity analyses confirmed the robustness of the results. The probability that the triple combination is cost effective was more than 90 % at a willingness-to-pay threshold of €18,000/QALY. This is the first study to evaluate the cost-utility of a single-pill triple combination. The single-pill V/A/H therapy is a cost-effective antihypertensive choice for the treatment of moderate to severe hypertension, compared to its dual components.

Physicians' perceptions and adherence to guidelines for the management of hypertension: a national, multicentre, prospective study.

Background. The aim of the current study was to investigate physicians' perceptions and adherence to the European guidelines for the management of hypertension. Methods. This is a national, multicentre, prospective, observational study, conducted between November 2007 and June 2008, in Cyprus. Consecutive hypertensive patients have been recruited by a random sample of physicians. The physicians' recommendations for every single patient have been recorded and compared with the 2007 ESH/ESC guidelines. Results. Of the total of 654 patients, 477 (72.9%) were correctly advised by their physician to receive antihypertensive treatment to control their blood pressure, while 396 (60.5%) correctly got advices to adopt only lifestyle changes. The overall adherence of physicians to the European guidelines (overall agreement rate) was 70.4% (k = 0.258, P < 0.001). Of the total of 68 physicians, 65 (95.6%) reported that they were aware of some guidelines. There was no statistically significant effect of specific physicians' characteristics on the overall adherence to guidelines, but there was in the percentage of patients achieving medication guidelines. Conclusions. The study demonstrated that although Cypriot physicians declared that they were aware of the clinical guidelines for the management of hypertension, more than one-fourth of high risk hypertensive patients remained untreated and 40% of low risk patients received inappropriate medication.

Telemonitoring in chronic heart failure: a systematic review.

Heart failure (HF) is a growing epidemic with the annual number of hospitalizations constantly increasing over the last decades for HF as a primary or secondary diagnosis. Despite the emergence of novel therapeutic approached that can prolong life and shorten hospital stay, HF patients will be needing rehospitalization and will often have a poor prognosis. Telemonitoring is a novel diagnostic modality that has been suggested to be beneficial for HF patients. Telemonitoring is viewed as a means of recording physiological data, such as body weight, heart rate, arterial blood pressure, and electrocardiogram recordings, by portable devices and transmitting these data remotely (via a telephone line, a mobile phone or a computer) to a server where they can be stored, reviewed and analyzed by the research team. In this systematic review of all randomized clinical trials evaluating telemonitoring in chronic HF, we aim to assess whether telemonitoring provides any substantial benefit in this patient population.

Quality of life measurement in patients with hypertension in Cyprus.

INTRODUCTION: Cardiovascular diseases and hypertension may have a significant impact on the quality of life of those who suffer from these conditions. The aim of the present study was to measure health-related quality of life among Cypriot patients suffering from hypertension and/or dyslipidaemia, as well as to investigate any temporal changes in their quality of life at 3 and 6 months from the initial visit. METHODS: A stratified random sampling method was used in this follow-up multi-centre study to select a representative sample of physicians who treat patients with hypertension in both public and private sector outpatient hospital clinics and physician offices. The participants were diagnosed by the physician according to the 2007 European guidelines for the management of arterial hypertension. The EQ-5D questionnaire was employed to measure self-assessed quality of life among these patients. Six hundred and fifty-four patients were recruited by physicians and agreed to participate, while 528 of them successfully completed EQ-5D at baseline and two subsequent phases (at 3 and 6 months), representing a response rate of 80.7%. RESULTS: A total of 39.6% of the respondents reported problems in one or more of the EQ-5D dimensions. This was more apparent in the case of anxiety and depression. There appeared to be statistically significant improvements with regard to mobility, usual activities, pain/discomfort and anxiety/depression dimensions between the initial visit and on first follow up, as well as subsequently. Median (interquartile range) EQ-5D index scores were 0.97 (0.19), 0.97 (0.19) and 0.97 (0.17) at first visit, first follow-up and second followup respectively (p<0.001). Also, median EQ-5D VAS scores were 80 (20), 85 (10) and 90 (15) at the initial, first follow-up and second follow-up visit respectively (p<0.001). Median EQ-5D VAS scores increased over time amongst all socio-demographic and risk groups of participants. CONCLUSION: Hypertension had little association with mobility and physical activities, indicating that performing physical activities was not limited by hypertension. However, hypertension seems to be more strongly related to anxiety and depression.

Effectiveness, safety and cost of drug substitution in hypertension.

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis.

BACKGROUND: Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus. STUDY DESIGN: Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009). SETTING & POPULATION: Patients with diabetes mellitus. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials. INTERVENTION: Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents. OUTCOMES: Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups. RESULTS: Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was -64.8% (95% CI, -75.6 to -53.9) and the WMD of changes in albumin-creatinine ratio was -24.8% (95% CI, -39.6 to -10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.6 units of standard deviation [SD]; 95% CI, -0.8 to -0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, -1.1 units of SD; 95% CI, -1.8 to -0.4). LIMITATIONS: Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available. CONCLUSIONS: Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

The controversial effects of thiazolidinediones on cardiovascular morbidity and mortality.

Cardiovascular morbidity and mortality in patients with type 2 diabetes are a major problem in clinical practice. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator-activated receptor gamma which improve glycaemic control by reducing insulin resistance. TZDs also seem to have beneficial effects on various cardiovascular risk factors and consequently may have the potential to reduce the risk of cardiovascular disease (CVD). Although the first large-scale clinical trial evaluating the effect of a TZD on secondary prevention of major adverse cardiovascular outcomes supported this hypothesis, a recently published meta-analysis raised substantial uncertainty about the cardiovascular safety of rosiglitazone. This article summarises the evidence from completed and ongoing outcome trials with TZDs, as well as the recent meta-analytic data on their cardiovascular safety, aiming to provide an up-to-date and balanced view of a very important field. Data from clinical trials consistently indicate that treatment with glitazones significantly increase the risk of heart failure. Despite the fact that rosiglitazone and pioglitazone have much more similarities than differences with regards to their effects on cardiovascular risk factors, pioglitazone seems to have more favourable effects on major cardiovascular outcomes. This issue also highlights the potential hazards involved in using surrogate end-points for drug approval.